Colchicine and thiocolchicine have been known for some time in the medical practice. Colchicine is used in the therapy of gout and related inflammatories states. 3-O-Demethylthiocolchicine glucoside is used as miorelaxant in spasticity and muscle pains due to contractures. However, in both cases the use of these compounds is limited due to their high toxicity.
Colchicine and thiocolchicine are also known antiblastic compounds, ie compounds that are able to destabilize the microtubules through interaction with tubuline. The possible use of a number of colchicine- and thiocolchicine-derivatives as antitumor medicaments has been studied. Due to their low therapeutic index none of them has been successful, with the sole exception of demecolchicine, introduced in therapy in the sixties for the treatment of leukemic forms and subsequently replaced by the more effective Vinca alkaloids.
WO 01/68597 discloses thiocolchicine dimers in which the thiocolchicine residues are liked through a linear aliphatic amido or amido-ureido bridge.